The specific aim of this project is to employ electrochemical and related analytical techniques to investigate the oxidation chemistry of a group of naturally occurring or otherwise biologically significant 3-substituted indoles. Among the compounds which will be investigated are tryptophan, 5-hydroxytryptamine, 5,6- and 5-7- dihydroxytryptamine, indole-3-acetic acid and various metabolities of these species. There is abundant literature evidence that these compounds undergo many oxidation reactions in living systems yet the mechanisms and products of these processes are not understood. In order to begin to understand the chemistry involved in such reactions a basic, fundamental study of the oxidation chemistry is required. It is believed that electrochemical and associated analytical methodologies provide the best techniques to study this oxidation chemistry. Our previous investigations have clearly shown that electrochemical studies of the oxidation and related chemistry of biological molecules can provide valuable insights into the biochemical oxidation mechanisms. It is expected that the planned studies on the oxidation chemistry of indoles will provide even more valuable information. It is planned to employ electrochemical and related techniques to define the redox potentials associated with the oxidation reactions of indoles, to chemically and physically characterize intermediates and to identify and quantitate products. Furthermore, it is hoped to develop an understanding of the interactions of putative oxidative intermediates such as quinones and quinoneimines with species commonly found in tissue. The ultimate goal of the proposed work is to provide a rational and systematic basis for understanding the oxidation chemistry of biologically significant indoles. This is turn should provide the basis for understanding the oxidation chemistry of indoles in living systems.